The American Joint Committee on Cancer (AJCC) tumor-node-metastasis (TNM) staging for all cancer sites has been updated periodically as a published manual for many years. The last update of the manual version, the eighth edition AJCC Cancer Staging Manual, went into use on January 1, 2018. The AJCC has since restructured and updated its processes for curating, analyzing, and publishing updates to the TNM staging system. All AJCC staging-related data are now housed on its new application programming interface. Consequently, the subsequent AJCC TNM staging updates are now published electronically as protocols and are released by disease sites. The protocol for carcinoma of the vulva, AJCC version 9, is now published. The new TNM vulvar cancer staging was validated using the American College of Surgeons' National Cancer Data Base. This article highlights the changes to the new AJCC TNM staging protocol for carcinoma of the vulva; these changes align with the 2021 International Federation for Gynecology and Obstetrics staging. The most important of the changes are: (1) a new method for depth of invasion measurement, (2) the addition of a new T subcategory-T4, (3) redefined N subcategories, and (4) an increased number of M subcategories with the addition of clinical to all M subcategories.
This article provides updated global cancer statistics for the year 2024 based on the GLOBOCAN estimates of the International Agency for Research on Cancer. The authors describe national cancer incidence and mortality by world region and the Human Development Index and predict the burden in 2050 based on demographic trends. In 2024, an estimated 20.6 million new cancer cases (19.5 million excluding nonmelanoma skin cancer) and 9.8 million deaths (9.7 million excluding nonmelanoma skin cancer) occurred worldwide, equivalent to one in five people developing cancer during their lifetime and one in nine men and one in 13 women dying from the disease. Lung cancer is the most frequently diagnosed cancer, responsible for almost 2.6 million new cases (12.8%), followed by female breast (11.8%), colorectal (9.9%), prostate (7.5%), and stomach (4.7%) cancer. Lung cancer is also the leading cause of cancer death, with an estimated 1.9 million deaths (19.1%), followed by colorectal (9.4%), liver (7.5%), female breast (7.1%), and stomach (6.6%) cancer. Incidence rates vary four- to five-fold across regions, with the highest rates found in Australia/New Zealand (men, 477 per 100,000; women, 396 per 100,000), whereas mortality rates differ two-fold, with elevated rates in Eastern Europe for men (158 per 100,000) and Melanesia for women (108 per 100,000). The incidence burden is predicted to reach 34.4 million by 2050, up 67% from 2024, with the largest proportional increases in lower Human Development Index countries. Although global variation in cancer profiles demands a nuanced approach to cancer control at national and regional levels, primary prevention must be at the forefront, including intensified efforts to reduce tobacco use, prevent infections, lower alcohol consumption and excess body weight, and increase physical activity.
Cancer advances are not distributed equitably among many segments of the population. Specifically, individuals with serious mental illness (SMI) face compounded disparities in cancer detection, treatment, and survival. SMI, characterized by conditions such as schizophrenia, bipolar disorder, and severe major depression, is associated with significant functional impairment and a two-to-three-decade reduction in life expectancy. Patients with SMI encounter unique challenges when navigating cancer care, including fragmented care pathways, less access to cancer therapeutics, limited psychosocial support, stigma, heightened vulnerability to diagnostic overshadowing where symptoms are attributed to their psychiatric rather than a medical or oncologic condition, and underrepresentation in therapeutic clinical trials. This review explores the intersection of SMI and cancer care starting with the conceptual background and its importance related to cancer outcomes and the delivery of ethical care to highlight unmet needs and a multitude of barriers. The paper proposes practical recommendations to improve cancer care for individuals with SMI who develop cancer including adopting the collaborative care model, enhancing psychosocial and psychiatric integration in oncology settings, and addressing biases inherent in clinician training. Interventions targeting individual, interpersonal, health system, and policy levels are essential to comprehensively mitigating disparities and developing durable cancer delivery strategies. Equitable cancer care for patients with SMI is both a moral imperative and a cornerstone of advancing social justice in oncology. Thus, there is a critical need to prioritize the translation of research advances, to close the gap in cancer outcomes and mortality, and to improve patient outcomes and wellbeing.
Extranodal natural killer (NK)/T-cell lymphoma (ENKTCL) is one of the most aggressive non-Hodgkin lymphomas characterized by NK-cell or T-cell origins, a geographic prevalence in Asian and South American populations, and Epstein-Barr virus (EBV) infection. ENKTCL used to be a fatal disease upon treatment with anthracycline-containing chemotherapies. However, the treatment paradigms for ENKTCL have evolved; consequently, patients have achieved significantly improved clinical outcomes. Today, combined-modality therapies co-targeting genomic instability and metabolic vulnerability comprise the standard of care for early stage ENKTCL, whereas therapies that include targeting of immune and metabolic dysregulation are the backbone of treatment for advanced-stage ENKTCL. New agents targeting surface antigens, oncogenic signaling pathways, and EBV are under investigation and have demonstrated promising responses. Hematopoietic stem cell transplantation is beneficial when used in therapy-responsive, high-risk patients and ENKTCL-associated hemophagocytic lymphohistiocytosis, but it is not recommended for early stage ENKTCL. Although nearly 80% of patients with newly diagnosed ENKTCL achieve long-term survival, treatment of relapsed/refractory ENKTCL is critical. Because it is now understood that EBV infection has a major role in disease progression, a deeper understanding of EBV-associated oncogenesis and alterations in the tumor microenvironment foster the development of novel therapeutic strategies, such as cellular therapies and vaccines targeting EBV. Future multicenter collaborations worldwide will be needed to further optimize mechanism-based treatment in the era of precision medicine, paving a curative pathway for this once fatal disease.
Systemic immunoglobulin light-chain amyloidosis is a rare but life-threatening plasma cell disorder characterized by the production of misfolded monoclonal light chains that deposit as amyloid fibrils, leading to pathologic tissue remodeling and progressive multiorgan dysfunction. Despite substantial therapeutic advances, delayed diagnosis remains common because of nonspecific presentations and the need for coordinated hematologic, pathologic, and organ-specific evaluation. The introduction of daratumumab-based regimens has transformed frontline therapy, whereas advances in cytogenetic profiling, measurable residual disease assessment, and transplantation strategies have informed risk-adapted management. Emerging treatments, including BCL-2-targeted therapy, bispecific antibodies, chimeric antigen receptor T-cell therapy, and possibly fibril-directed approaches, further expand the therapeutic landscape. This review summarizes contemporary concepts in the pathobiology, diagnosis, and management of systemic light-chain amyloidosis, with an emphasis on practical diagnostic algorithms, evolving response assessment, and remaining challenges in achieving durable organ recovery and sustained survival.
Colorectal cancer (CRC) is a leading cause of cancer incidence and mortality in the United States, with rates recently increasing among adults younger than 65 years. In 2018, the American Cancer Society (ACS) lowered the recommended age to initiate screening for average-risk adults to age 45 years. Since then, new molecular-based screening tests-a multitarget stool RNA test (mt-sRNA), a next-generation mt-sDNA test, and a blood-based cell-free DNA assay-have received regulatory approval for CRC screening. For this update, the ACS Guideline Development Group commissioned a targeted, systematic evidence review evaluating diagnostic performance and published modeling studies to judge the potential impact of these tests on CRC incidence and mortality. The ACS reaffirms the recommendation that average-risk adults should initiate CRC screening at age 45 years and continue through age 75 years for those with a life expectancy greater than 10 years. Consistent with prior guidelines, the ACS emphasizes that offering multiple, recommended screening options supports informed patient choice and may improve participation, because the most effective screening test is the one that the patient completes. The next-generation mt-sDNA test, which is an updated version of an already recommended mt-sDNA test, and the mt-sRNA test demonstrated high sensitivity for CRC and moderate sensitivity for advanced precancerous lesions and are recommended, along with annual high-sensitivity fecal immunochemical and high-sensitivity guaiac-based fecal occult blood tests, as preferred stool-based screening options at 3-year intervals. Compared with established stool-based tests, blood-based tests demonstrated lower sensitivity for both advanced precancerous lesions and stage I cancers, with modeling studies predicting less effectiveness in reducing CRC incidence and mortality. At this time, blood-based tests should be recommended only to individuals who decline or do not complete preferred screening tests. Ongoing evaluation of adherence, real-world implementation, and clinical outcomes will inform future updates for these new tests. For screening to be effective, a positive result on any noncolonoscopy screening test requires timely follow-up with colonoscopy, preferably within 6 months, to complete the screening process.
European Organization for Research and Treatment of Cancer trial EORTC 22922/10925 evaluated internal mammary and medial supraclavicular (IM-MS) lymph node irradiation (IM-MS-RT) in patients with stage I-III breast cancer. Eligible patients had involved axillary nodes and/or centrally/medially located tumors regardless of nodal involvement. The primary end point was overall survival, secondary end points were disease-free survival, distant metastases-free survival, breast cancer mortality, and any breast recurrence. Between 1996 and 2004, 4004 patients were randomized. The median patient age was 54 years. At a median follow-up of 22.2 years, 1550 (38.7%) patients died, of whom 796 (51.4%) died from breast cancer. At 20 years, the overall survival rate was 61.8% in the control group versus 61.0% in the IM-MS-RT group (hazard ratio [HR], 1.00; p = .967); the disease-free survival rate was 49.0% versus 48.2%, respectively (HR, 0.97; p = .515); and the distant metastases-free survival rate was 59.8% versus 58.9%, respectively (HR, 0.97; p = .578). The breast cancer mortality rate was 22.4% in the control group and 18.6% in the IM-MS-RT group (HR, 0.82; p = .006), whereas the rate of deaths not from breast cancer or from unknown causes was 15.8% versus 20.4%, respectively (HR, 1.26; p = .002). Lung fibrosis, cardiac fibrosis, and cardiac diseases were more frequent after IM-MS-RT versus no IM-MS-RT (6.3% vs. 3.2%, 2.7% vs. 1.7%. and 15.2% vs. 11.7%, respectively); and the rates of severe cardiac and lung morbidities (scores of 3 or 4) were 1.9% versus 1.7% and 0.3% versus 0.0%, respectively. Breast cancer mortality at 20 years was statistically significantly lower after IM-MS-RT, but deaths not from breast cancer increased after 15 years, resulting in no long-term benefit of IM-MS-RT on overall survival. Therefore, the authors strongly call for very long-term follow-up of treatments for prognostically favorable cancers such as breast cancer.
As more cancer treatments take place in outpatient settings, family caregivers provide essential care and emotional support over long periods. Unaddressed patient and caregiver psychological distress can lead to worse outcomes, reflecting the challenges of managing complex care demands in the home setting. This systematic review and meta-analysis examined how well nonpharmacologic interventions (NPIs) reduce distress, anxiety, and depression in adult patients with solid tumors and their family caregivers. The authors included 68 randomized controlled trials (RCTs) with a total of 11,987 participants. NPIs were characterized as psychoeducation, therapeutic counseling, skills training, or behavior modification. By using random-effects models (Hedges g), they observed that NPIs significantly reduced patient distress at both 0.0-3.0 months (g = 0.13) and 3.1-6.0 months (g = 0.18), but NPIs did not significantly reduce caregiver distress. In the short term (0.0-3.0 months), NPIs also significantly reduced anxiety (g = 0.31 for patients; g = 0.15 for caregivers) and depression (g = 0.28 for patients; g = 0.25 for caregivers). Subgroup analyses examined the impact of patient and caregiver characteristics along with NPI type, delivery format, dose, and duration. NPIs delivered jointly to patients and caregivers yielded significant effects that were higher compared with NPIs delivered separately. NPIs can help manage distress in patients and reduce anxiety and depression in both patients and caregivers. However, the lack of long-term follow-up limits our understanding of their impact on patients and caregivers with prolonged or delayed psychological symptoms (PROSPERO registration number CRD42024536629).
Third-generation epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) are standard first-line therapy for advanced, EGFR-mutated nonsmall cell lung cancer (NSCLC). However, their benefit is limited in patients who have co-existing tumor suppressor gene (TSG) mutations, highlighting a need for intensified strategies to improve outcomes. ACROSS2 (ClinicalTrials.gov identifier NCT04500717) is the first prospective, multicenter, randomized phase 3 study to compare the third-generation EGFR-TKI aumolertinib in combination with carboplatin-pemetrexed versus aumolertinib monotherapy in patients who had NSCLC with EGFR mutations and concomitant TSG mutations. In total, 126 patients were enrolled and randomly assigned to either combination therapy (n = 62) or monotherapy (n = 64). The primary end point was median progression-free survival (PFS). At a median follow-up of 25.3 months, combination therapy significantly prolonged median PFS compared with monotherapy (19.78 vs 16.53 months; hazard ratio, 0.58; 95% confidence interval, 0.34-0.97). Landmark PFS rates at 12, 18, and 24 months were 78.7% versus 65.3%, 67.2% versus 40.8%, and 41.0% versus 29.9%, respectively. Subgroup analyses demonstrated a clear PFS benefit in patients who had co-existing tumor protein p53 (TP53) mutations. Grade 3 or greater adverse events occurred in 25.9% of patients who received combination therapy versus 17.2% of those who received monotherapy; no drug-related deaths were observed. Overall survival data were immature (data maturity, 4%). The ACROSS2 trial provides the first prospective evidence supporting a genotype-directed, chemotherapy-targeted intensification approach favoring aumolertinib plus carboplatin-pemetrexed for this molecularly defined population.
Genomics-and genomic testing in particular-has transformed oncology, facilitating both targeted therapies and personalized care. In pediatric oncology, unique clinical and ethical considerations arise. Compared with adults, children and adolescents are affected by more limited evidence regarding test performance, variant interpretation, and the clinical utility of genomically informed interventions. Nevertheless, genomic findings may have implications beyond the patient, affecting their parents, siblings, and other relatives and raising questions around consent, assent, privacy, and psychosocial impact. This narrative review examines how ethical dimensions of genetic and genomic testing evolve across the pediatric cancer continuum, from diagnosis and treatment through survivorship and transition to adult care. Attention is given to communication strategies, interdisciplinary support, and equity concerns that influence the responsible integration of genomic medicine. The authors also identify priority areas for future inquiry, including incorporation of children's perspectives, longitudinal approaches to recontact and reconsent, and better understanding of how genomic information affects treatment decision-making. Pediatric genetic and genomic testing in oncology holds great promise, but its benefits can only be realized through thoughtfully developed and standardized communication practices, careful ethical deliberation, and equitable implementation. By proactively addressing these issues, pediatric oncologists can harness genomic advances in ways that respect and support children and their families.
Colorectal cancer (CRC) is the second most common cancer-related death in the United States and ranks first in adults younger than 50 years. Every 3 years, the American Cancer Society reports on CRC occurrence based on incidence from population-based cancer registries and mortality from the National Center for Health Statistics. Overall, CRC incidence declined by 0.9% annually during 2013-2022 driven by decreases of 2.5% annually in adults aged 65 years and older. In sharp contrast, incidence rates increased by 3% annually in adults aged 20-49 years and by 0.4% annually in adults aged 50-64 years dominated by tumors in the distal colon and rectum. Consequently, overall rectal cancer incidence increased by 1% annually from 2018 to 2022 after decades of decline and now accounts for 32% of all CRC, up from 27% in the mid-2000s. Increasing CRC incidence in adults aged 50-64 years was confined to regional and distant-stage diagnosis (1.1%-1.3% annually during 2013-2022), likely contributing to an upturn in mortality in this age group of 1% annually since 2019 that was steepest (2.3% annually) in White individuals. Mortality has increased in adults younger than 50 years by 1% annually since 2004, whereas rates have decreased in adults 65 years and older by 2.3% annually since 2012. Despite steady progress for older adults, both CRC incidence and mortality are increasing in adults younger than 65 years who are in the prime of life, underscoring an urgent need for etiologic research to discover the cause of the rising trend. Meanwhile, morbidity and mortality could be mitigated with earlier diagnosis, through screening and educating clinicians and the general public about CRC symptoms, and greater attention to the unique needs of younger patients, including discussion about the preservation of fertility and sexual health.
Reliable, contemporary estimates of the global childhood cancer burden remain scarce, particularly in the post-coronavirus disease 2019 (COVID-19) era. By using data from the Global Burden of Disease 2021 and Global Cancer Observatory 2022 projects, the authors evaluated the childhood cancer burden at global, regional, and national levels, characterizing temporal and projected trends, and analyzed the data according to disparities by geography and socioeconomic development. From 2000 to 2021, the age-standardized incidence rate (ASIR) and the age-standardized mortality rate (ASMR) of childhood cancer declined overall (average annual percent change, -0.88 and -2.13, respectively), especially during the COVID-19 pandemic. During this period, the disparities in childhood cancer burden were mainly concentrated in countries/territories with a lower Sociodemographic Index. In 2022, an estimated 202,164 new cases and 77,182 deaths from childhood cancer occurred worldwide (ASIR and ASMR, 10.3 and 3.9 per 100,000 children, respectively). Countries/territories with higher a Human Development Index (HDI) had a higher incidence (ASIR, 8.0 [low HDI] vs. 15.3 [very high HDI] per 100,000), whereas those with a lower HDI had higher mortality (ASMR, 4.4 [low HDI] vs. 2.8 [very high HDI] per 100,000). Analyses indicated that, by 2050, there will be 204,925 projected new cases and 78,210 deaths globally, with increases only in low HDI countries/territories, exacerbating existing health inequities. Childhood cancer remains a global health challenge, with notable geographic and socioeconomic disparities. These data serve as the impetus for governments and policymakers to prioritize resources and equitable access to interventions, particularly in regions with lower levels of development, while addressing health care vulnerabilities exposed by global crises like the COVID-19 pandemic.
